Detecting drug resistance at the time of TB diagnosis

Dr Sarabjit Chadha

The Union

Drug resistance TB

Resistance to anti-TB drugs

MDR TB resistance to Rifampicin and Isoniazid

XDR TB MDR TB plus resistance to quinolones and second line injectables

Poor treatment outcomes

Burden of MDR TB

Globally* Annually 3.5% of new; 20% of previously treated TB cases have MDR TB

~480,000 MDR cases annually

Annually ~210,000* deaths occur due to MDR- TB

* WHO Global TB Report 2014

Patient presents with symptoms of TB

Smear microscopy X ray (Drug resistance usually not tested)

Diagnosed as TB and initiated on treatment for drug sensitive TB (6 mths)

Fails treatment; put on re-treatment regimen (8 mths) (Drug resistance not tested)

Fails treatment again

Tested for drug resistance

Cured

Treated for DR-TB

Delay of ~12 months before diagnosis of drug resistance

Most of the patients will not survive the delay and inappropriate treatment especially if there are co-morbidities like HIV, Diabetes

The prolonged suffering (and maybe death) can be avoided if testing for DR-TB is done early

Why early diagnosis of DR-TB is important ?

Patient is given inappropriate treatment Prolongs suffering and morbidity

Enhances severity of disease- mortality

Amplify resistance (more difficult to treat)

Treatment interruption

Seek alternate care

Transmission to others continues

Most of these are avoidable if diagnosis is made early and appropriate treatment given

Reasons for delay and changing scenario

Smear microscopy does not detect resistance

Earlier the only option was culture and DST

3-4 months to give results

Requires laboratory infrastructure and skilled workers

Funds and political commitment

Newer rapid molecular tests the situation has changed

Xpert MTB/RIF (CBNAAT)

Results in less than 2 hours

Automated

No special infrastructure required

Diagnose both TB and Rifampicin resistance together

India- Case study

Highest TB and MDR TB burden globally 2% of new and 15% of those with previous

history of TB are MDR TB* ~62000 MDR cases annually

Initiated MDR-TB services in 8 districts in 2007 (20 m pop)

Expanded to the entire country (700 districts) in 2013 (1.2 billion pop)

Starting with 4 labs in 2007 there are today 62 labs with culture & DST facilities 50 with Line Probe Assay 89 Xpert MTB/RIF (CBNAAT) sites

* WHO Global TB Report 2014

Progress 2007-2014

109

2341

4297

25562

309 8144 17696

255408

0

5000

10000

15000

20000

25000

30000

0

50000

100000

150000

200000

250000

300000

2007 2008 2009 2010 2011 2012 2013 2014

Number tested for MDR-TB Diagnosed as MDR TB Initiated on treatment

18 LPA 18 Xpert 36 CDST labs

50 LPA 89 Xpert 69 CDST labs

9 CST labs

4 CDST labs

Plan ahead

Universal DST for all TB cases by 2019 Ambitious plan

Set up 120 culture and DST labs

950 CBNAAT (Xpert or similar technology) sites

Over 1 million DST annually

Provide testing for second line drug resistance

Treatment for all diagnosed at least 60,000 MDR cases annually

Improving treatment outcomes Currently ~50% to 65%

Saving additional lives

Moving towards early diagnosis of DR-TB

2007

4 Culture and DST laboratories

Failures of retreatment cases

2011

36 labs; 18 LPA; 18 Xpert (CBNAAT) sites

All Failures; PLHIV, contacts of MDR TB

2014

62 labs; 50 LPA; 89 Xpert (CBNAAT) sites

All failures, All retreatment cases, PLHIV, contacts MDR

2019

120 labs; 950 Xpert (CBNAAT) sites

All TB cases tested for drug resistance at diagnosis

All MDR cases tested for second line drug resistance

Challenges

Cost of the Xpert MTB/RIF machines (~20,000 $) and cost per test is still high (10 $) Additional funds and political commitment

Diagnosis of resistance to second line drugs pre- XDR and XDR TB)

Currently by liquid culture which require accredited labs

No automated convenient tests like Xpert available

Matching treatment capacity

Enhance treatment adherence Psycho-social-economic support

Shorter drug regimens

Prevention of MDR TB

Thank you